Post-COVID-19 Cholangiopathy: A Recent Indication for Liver Transplantation

Since its discovery in the late 2019 in Wuhan city, China, coronavirus disease 2019 (COVID-19) rapidly became a major public health problem, with more than 5 million deaths at 2 years of follow-up [1, 2]. Furthermore, COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), has been associated with a considerable morbidity as well [3]. Although COVID-19 is known as a predominantly respiratory tract infectious disease, with fever, fatigue, cough and dyspnea being the most common presenting symptoms, SARS-CoV-2 has the ability to affect and damage other organ systems [4]. To gain cellular entry, this virus uses angiotensin-converting enzyme 2 (ACE2) as a cell receptor [5]. In addition to the lungs, the aforementioned receptors are highly expressed in the gastrointestinal (GI) tract, kidneys, liver and biliary tree, pancreas, arterial smooth muscle cells and vascular endothelial cells [5]. The expression of ACE2 receptors in the previously mentioned systems raises the possibility of COVID-19-induced multi-organ system [6]. When affected, they are referred to as extra-pulmonary complications of COVID-19. Extra-pulmonary complications postCOVID-19 infections are more common in critically and severely ill patients [4]. Liver and biliary complications following COVID-19 infection were firstly reported by Huang et al [7], when he noticed an elevated level of liver function tests (LFTs), especially in patients with critically ill COVID-19. Almost 20% of patients with COVID-19 infection have elevated liver enzymes, which can predict disease outcome [8]. The current literature has demonstrated that liver injury is more common in patients with critical COVID-19 and pre-existing chronic liver disease, such as cirrhosis, and in those who have other coexisting causes of liver damage, such as the use of potentially hepatotoxic therapies [9, 10]. The mechanisms by which COVID-19 causes damage to the liver are diverse and include, among others, direct hepatocellular injury (the main injury pattern) and cholestatic pattern, referred to as “post-COVID-19 cholangiopathy” (PCC) [11, 12]. PCC, previously known as secondary sclerosing cholangitis in critically ill patients due to severe COVID-19 infection, is a newly introduced entity gaining medical attention worldwide. It is characterized by severe cholestasis and ongoing jaundice that persist long after renal and pulmonary recovery. Although PCC is a well-known extra-pulmonary manifestation post-COVID-19 infection, data regarding this specific entity, mainly mechanism of injury and therapeutic options, are still vague and not clear.